To produce "one" effective compound may require a bench chemist to react hundreds of compounds to form a library of compounds which is then extensively tested to discover that "one" most effective compound suited for a particular use, such as, for example an insecticide. One approach is to conduct such a general synthesis through the use of combinatorial chemistry. The technique of combinatorial chemistry permits one to simultaneously form large "libraries" of compounds en masse, in identifying the most promising "lead" compounds instead of synthesizing compounds one by one, as has been done traditionally. Such libraries of compounds are then screened to disclose the most effective compound for a particular use by high-throughput screening of these libraries. Thus, combinatorial organic synthesis (COS) is not random but systematic and repetitive use of sets of chemical "building blocks" for forming a diverse set of molecular entities. The combinatorial chemistry is a technologically advanced way of finding a proverbial "needle in a haystack". The approach is to remove the guesswork and instead, create and test as many compounds or mixtures as possible--logically and systematically--to obtain a viable set of active leads. Such combinatorial techniques have become very useful in producing small organic molecules with molecular weights of up to 1000, a molecular range in which drugs are generally found. Some of the common approaches to COS, include:
Systematic reaction of arrayed, spatially addressable building blocks in individual reaction wells or positions that form separated "discrete" molecules. Active compounds are identified by their location on the grid. Another technique, known as encoded mixture synthesis, uses nucleotide, peptide, or other types of more inert chemical tags to identify each compound. In yet another approach, a series of compound mixtures are synthesized combinatorially during deconvolution, each time fixing some specific structural feature. Each mixture is assayed as a mixture and the most active combination is then analyzed. Further rounds of synthesis systematically fix other structural features until a manageable number of discrete structures are synthesized and screened. Scientists working with peptides, for example, can use deconvolution to optimize or locate, the most active peptide sequence from millions of possibilities.
However, none of the devices or methods suitable for the multiple, simultaneous synthesis of peptides or oligonucleotides are useful in synthesizing general compounds. Among the many special problems found in the synthesis of general compounds, as opposed to peptide or oligonucleotide synthesis, is the problem of providing a device that accommodates the wide range of systematic manipulations required for synthesis of general compounds. The currently available devices, for example, have serious limitations in terms of:
lack of versatility, such as addition of solids in the midst of a reaction, difficulty in readily accessing the reactor contents without interrupting inert atmosphere, stirring, or heating/cooling of many of the neighboring reaction vessels; PA1 lack of compactness, thereby requiring considerable laboratory space; PA1 lack of scalability, since the conventional devices lack means such as, heating/cooling, mixing, or reagent addition; and PA1 lack of openness of architecture, which hampers the possibility of using adjunctive equipment, such as overhead stirring, spectroscopic probes, photochemical lamps, and sonicators. PA1 a tank having located therein a plurality of reaction vessels supported by a reaction vessel mounting plate positioned inside said tank; PA1 a plurality of lid blocks detachably mounted atop said tank whereby each said lid block selectively engages or disengages an adjacently located row of said reaction vessels; and PA1 a lid block lifter means for lowering or raising each said lid block to respectively sealably engage or disengage from said adjacently located row of said reaction vessels, such that said adjacently located row of said reaction vessels is exposed when said lid block lifter means are disengaged from said adjacently located row of said reaction vessels. PA1 charging a plurality of reaction vessels positioned in a tank with one or more reactants; PA1 sweeping each said reaction vessel with an inert gas therethrough to remove air therefrom; PA1 conveying desired amounts of one or more reagents to each said reaction vessel; PA1 heating said plurality of reaction vessels to a desired reaction temperature; PA1 agitating the reactor contents in each said reaction vessel at a desired rate of agitation for a desired duration to produce reaction products in said plurality of said reaction vessels; and PA1 removing said reaction products from said plurality of said reaction vessels.
Additionally, procedures adjunctive to the synthesis of general compounds, such as distillation, evaporation, and in certain cases, crystallization, would not be possible, or would be very difficult with the current devices. As a result, these current devices are restricted to parallel or combinatorial synthesis that takes place under uniform non-varying conditions.
Cody et al. (hereafter Cody) in U.S. Pat. No. 5,324,483 attempted to provide for an apparatus in which multiple, simultaneous synthesis of general compounds could be conducted. The apparatus of Cody consists of a reservoir block having a plurality of wells, a plurality of reaction tubes, having filters at their ends, holder block having a plurality of apertures; and a manifold which may have ports for introduction/maintenance of a controlled environment.
However, the simultaneous synthesis of general compounds often takes place under varied non-uniform conditions requiring ready access to various reaction vessels without interrupting the ongoing reactions occurring in adjacent reaction vessels. The prior art devices, including that of Cody, fail to allow the user such ready access. The apparatus and the method of the present invention solves the problem of access by providing means that permit such access.
Furthermore, the varied non-uniform reaction conditions generally required for the simultaneous synthesis of general compounds are typically monitored in real time with independent individual control of the reaction conditions at each reaction vessel location. The prior art devices, including that of Cody, are unsuitable for use under these special conditions required for general synthesis. The apparatus and the method of the present invention solves the problem of lack of real time monitoring and independent control of the reaction conditions at each reaction location by providing the user with means to conduct multiple, simultaneous synthesis of general compounds by simultaneously, independently and individually controlling the varied conditions in each reactor vessel location in real time.